BACKGROUND: This is a multicentre, European, prospective trial evaluating the diagnostic accuracy of One Step Nucleic Acid Amplification (OSNA) compared to sentinel lymph nodes histopathological ultrastaging in endometrial cancer patients. METHODS: Centres with expertise in sentinel lymph node mapping in endometrial cancer patients in Europe will be invited to participate in the study. Participating units will be trained on the correct usage of the OSNA RD-210 analyser and nucleic acid amplification reagent kit LYNOAMP CK19 E for rapid detection of metastatic nodal involvement, based on the cytokeratin 19 (CK19) mRNA detection. Endometrial cancer patients ≥ 18 years listed for surgical treatment with sentinel lymph node mapping, with no history of other types of cancer and who provide a valid written consent will be considered potentially eligible for the study. However, they will only be enrolled if a successful sentinel lymph node mapping is retrieved. Each node will be processed according to the study protocol and assessed by both OSNA and ultrastaging. DISCUSSION: The accuracy of OSNA (index test) will be assessed against sentinel lymph node histopathological ultrastaging (reference test). This European study has the potential to be the largest study on the use of OSNA in endometrial cancer to date. OSNA could represent a modern diagnostic alternative to sentinel lymph node ultrastaging with the added benefits of standardisation and fast results. TRIAL REGISTRATION: The study was registered in the German Clinical Trial Register - Nr. DRKS00021520, registration date 25th of May 2020, URL of the trial registry record: https://drks.de/search/en/trial/DRKS00021520 .

• MeSH
• biopsie sentinelové lymfatické uzliny metody   MeSH
• keratin-19 genetika   MeSH
• lidé MeSH
• lymfatické metastázy * diagnóza   patologie   MeSH
• lymfatické uzliny patologie   MeSH
• multicentrické studie jako téma MeSH
• nádory endometria * patologie   genetika   diagnóza   MeSH
• prospektivní studie MeSH
• sentinelová uzlina * patologie   MeSH
• staging nádorů MeSH
• techniky amplifikace nukleových kyselin * metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Evropa MeSH

Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‐associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‐expression of keratins‐8/‐14 in the EM‐G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‐8, ‐14, ‐18, ‐19) and epithelial‐mesenchymal transition‐associated markers (SLUG, SNAIL, ZEB1, E‐/N‐cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‐A and MFGE8 attenuated the modulatory effect of CAFs on EM‐G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‐G3 cells in vitro. CAFs of different origins support the pro‐inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.

• MeSH
• antigeny povrchové MeSH
• fibroblasty asociované s nádorem * metabolismus   MeSH
• fibroblasty metabolismus   MeSH
• keratiny genetika   metabolismus   MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• MFC-7 buňky MeSH
• mléčné bílkoviny genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí genetika   MeSH
• nádory prsu * farmakoterapie   genetika   metabolismus   MeSH
• prognóza MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Colorectal cancer (CRC) is a leading global cause of illness and death. There is a need for identification of better prognostic markers beyond traditional clinical variables like grade and stage. Previous research revealed that abnormal expression of cytokeratin 7 (CK7) and loss of the intestinal-specific Special AT-rich sequence-binding protein 2 (SATB2) are linked to poor CRC prognosis. This study aimed to explore these markers' prognostic significance alongside two extraintestinal mucins (MUC5AC, MUC6), claudin 18, and MUC4 in 285 CRC cases using immunohistochemistry on tissue microarrays (TMAs). CK7 expression and SATB2-loss were associated with MUC5AC, MUC6, and claudin 18 positivity. These findings suggest a distinct "non-intestinal" immunohistochemical profile in CRC, often right-sided, SATB2-low, with atypical expression of CK7 and non-colorectal mucins (MUC5AC, MUC6). Strong MUC4 expression negatively impacted cancer-specific survival (hazard ratio = 2.7, p = 0.044). Genetic analysis via next-generation sequencing (NGS) in CK7 + CRCs and those with high MUC4 expression revealed prevalent mutations in TP53, APC, BRAF, KRAS, PIK3CA, FBXW7, and SMAD4, consistent with known CRC mutation patterns. NGS also identified druggable variants in BRAF, PIK3CA, and KRAS. CK7 + tumors showed intriguingly common (31.6%) BRAF V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.

• MeSH
• dospělí MeSH
• fenotyp MeSH
• fosfatidylinositol-3-kinasy třídy I genetika   metabolismus   MeSH
• imunohistochemie * MeSH
• keratin-7 metabolismus   genetika   MeSH
• kolorektální nádory * genetika   patologie   metabolismus   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mucin 4 genetika   metabolismus   MeSH
• mucin 5AC genetika   metabolismus   MeSH
• mucin 6 genetika   metabolismus   MeSH
• mutace MeSH
• nádorové biomarkery * genetika   metabolismus   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktory MeSH
• vazebné proteiny DNA v oblastech připojení k matrix * genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis. PATIENTS AND METHODS: This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival. RESULTS: Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413. CONCLUSION: The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.

• MeSH
• antigen CA-19-9 * krev   MeSH
• antigeny nádorové krev   MeSH
• dospělí MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• karcinoembryonální antigen * krev   MeSH
• keratin-19 krev   MeSH
• keratiny krev   MeSH
• kolorektální nádory * krev   diagnóza   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * krev   MeSH
• peptidy MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thymidinkináza * krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study. METHODS AND RESULTS: We complied a total of 24 myoepitheliomas with syncytial growth from our files. The tumors occurred in 12 male and 12 female patients (M:F = 1:1), with a median age of 31 years (range, 9-69 years). While the majority of tumors (75%, n = 18) occurred in skin, a significant subset (25%, n = 6) arose in non-cutaneous sites, including bone (n = 3), bronchus/trachea (n = 2), and interosseous membrane of tibia/fibula (n = 1). Tumor size ranged from 0.4 to 5.9 cm. Clinical follow-up (7 patients; range 14-202 months; median 56.5 months) showed a single local recurrence 8 years after incomplete skin excision but no metastases; all patients were alive at the time of last follow-up without evidence of disease. Histologically, all tumors were pink at low-power and characterized by a syncytial growth of bland ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm and prominent perivascular lymphoplasmacytic inflammation. One-third displayed adipocytic metaplasia (8/24). Rare cytologic atypia was seen but was not associated with increased mitotic activity. All tumors expressed S100, SMA, and/or EMA. Keratin expression was absent in most cases. Molecular analysis was performed in 16 cases, all showing EWSR1-rearrangments. In total, 15/15 (100%) harbored an EWSR1::PBX3 fusion, whereas 1 case EWSR1 FISH was the only molecular study performed. CONCLUSION: Syncytial myoepithelioma is a rare but recognizable morphologic variant of myoepithelioma which may have a predilection for skin but also occurs in diverse non-cutaneous sites. Our series provides evidence supporting a reappraisal of the term "cutaneous syncytial myoepithelioma," as 25% of patients in our series presented with non-cutaneous tumors; thus, we propose the term "syncytial myoepithelioma" to aid pathologist recognition and avoidance of potentially confusing terminology when referring to non-cutaneous examples. The behavior of syncytial myoepithelioma, whether it arises in cutaneous or non-cutaneous sites, is indolent and perhaps benign with a small capacity for local recurrence.

• MeSH
• dítě MeSH
• dospělí MeSH
• keratiny MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myoepiteliální nádor * patologie   MeSH
• nádorové biomarkery analýza   MeSH
• nádory glandulární a epitelové * MeSH
• nádory kůže * patologie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• diagnostické techniky molekulární metody   MeSH
• keratin-19 MeSH
• kohortové studie MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické metastázy diagnóza   MeSH
• mastektomie MeSH
• nádory prsu * chirurgie   diagnóza   MeSH
• stupeň nádoru MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.

• MeSH
• antigeny CD274 genetika   metabolismus   MeSH
• keratin-7 genetika   MeSH
• kolorektální nádory * patologie   MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• prognóza MeSH
• transkripční faktory genetika   MeSH
• vazebné proteiny DNA v oblastech připojení k matrix * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The diagnosis of solid tumors of epithelial origin (carcinomas) represents a major part of the workload in clinical histopathology. Carcinomas consist of malignant epithelial cells arranged in more or less cohesive clusters of variable size and shape, together with stromal cells, extracellular matrix, and blood vessels. Distinguishing stroma from epithelium is a critical component of artificial intelligence (AI) methods developed to detect and analyze carcinomas. In this paper, we propose a novel automated workflow that enables large-scale guidance of AI methods to identify the epithelial component. The workflow is based on re-staining existing hematoxylin and eosin (H&E) formalin-fixed paraffin-embedded sections by immunohistochemistry for cytokeratins, cytoskeletal components specific to epithelial cells. Compared to existing methods, clinically available H&E sections are reused and no additional material, such as consecutive slides, is needed. We developed a simple and reliable method for automatic alignment to generate masks denoting cytokeratin-rich regions, using cell nuclei positions that are visible in both the original and the re-stained slide. The registration method has been compared to state-of-the-art methods for alignment of consecutive slides and shows that, despite being simpler, it provides similar accuracy and is more robust. We also demonstrate how the automatically generated masks can be used to train modern AI image segmentation based on U-Net, resulting in reliable detection of epithelial regions in previously unseen H&E slides. Through training on real-world material available in clinical laboratories, this approach therefore has widespread applications toward achieving AI-assisted tumor assessment directly from scanned H&E sections. In addition, the re-staining method will facilitate additional automated quantitative studies of tumor cell and stromal cell phenotypes.

• MeSH
• barvení a značení MeSH
• deep learning * MeSH
• eosin MeSH
• epitelové buňky MeSH
• hematoxylin MeSH
• keratiny * MeSH
• lidé MeSH
• umělá inteligence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We assessed the value of cytokeratin 17 (CK17) expression for the differential diagnosis between primary ovarian mucinous tumors and metastases from the gastrointestinal tract (GIT) and the significance of CK17 expression in a broad spectrum of primary ovarian tumors with respect to their prognosis. The sample set consisted of 554 primary ovarian tumors and 255 GIT tumors. In the primary ovarian tumors, a higher CK17 expression (in > 10% of tumors cells) was present only in 0-11.4% of all tumors (including mucinous tumors, micropapillary serous borderline tumors, clear cell, endometrioid, and high-grade serous carcinomas). The only exception was low-grade serous carcinoma, where higher CK17 expression was present in 24% of cases. Concerning GIT tumors, the higher levels of CK 17 expression (in > 10% of tumor cells) were observed in the upper GIT tumors (68.5% of pancreatic ductal adenocarcinoma, 61.6% of gallbladder adenocarcinoma, and 46% of gastric adenocarcinoma), which differs substantially not only from most of the primary ovarian tumors, but also from colorectal carcinoma (3.7%; p < 0.001). The results of our study suggest that expression of CK17 can potentially be used as an adjunct marker in differential diagnosis between primary ovarian mucinous tumors and metastases from the upper GIT, but not from colorectal carcinoma. However, in GIT tumors, CK17 can be used in the differential diagnosis between adenocarcinomas of the upper and lower GIT. Statistical analysis did not reveal strong association of CK17 expression with clinicopathological variables or patient outcomes in any primary ovarian tumors.

• MeSH
• adenokarcinom * diagnóza   MeSH
• diferenciální diagnóza MeSH
• gastrointestinální nádory * diagnóza   MeSH
• imunohistochemie MeSH
• keratin-17 MeSH
• kolorektální nádory * diagnóza   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinivky břišní * diagnóza   MeSH
• nádory vaječníků * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The coordinated interplay of cytoskeletal networks critically determines tissue biomechanics and structural integrity. Here, we show that plectin, a major intermediate filament-based cytolinker protein, orchestrates cortical cytoskeletal networks in epithelial sheets to support intercellular junctions. By combining CRISPR/Cas9-based gene editing and pharmacological inhibition, we demonstrate that in an F-actin-dependent context, plectin is essential for the formation of the circumferential keratin rim, organization of radial keratin spokes, and desmosomal patterning. In the absence of plectin-mediated cytoskeletal cross-linking, the aberrant keratin-desmosome (DSM)-network feeds back to the actin cytoskeleton, which results in elevated actomyosin contractility. Also, by complementing a predictive mechanical model with Förster resonance energy transfer-based tension sensors, we provide evidence that in the absence of cytoskeletal cross-linking, major intercellular junctions (adherens junctions and DSMs) are under intrinsically generated tensile stress. Defective cytoarchitecture and tensional disequilibrium result in reduced intercellular cohesion, associated with general destabilization of plectin-deficient sheets upon mechanical stress.

• MeSH
• aktiny metabolismus   MeSH
• biomechanika MeSH
• buňky MDCK MeSH
• cytoskelet metabolismus   ultrastruktura   MeSH
• desmozomy metabolismus   ultrastruktura   MeSH
• epitelové buňky metabolismus   ultrastruktura   MeSH
• genový knockout MeSH
• keratiny metabolismus   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši MeSH
• pevnost v tahu MeSH
• plektin metabolismus   MeSH
• protein - isoformy metabolismus   MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH